The primary objective of this research project is to learn more about the activation process in heart muscle, i.e., the chain of reactions which couples the action potential at the outer cell membrane to the contractile system inside the cell. We are now working with several kinds of heart muscle and determining the effects on transmembrane action potentials of various factors which influence contraction strength, such as pattern of stimulation, concentrations of K, Na, and Ca ions, and of acetylcholine, epinephrine, tetrodotoxin, and ryanodine. When possible we will analyze the effects on action potentials in terms of changes in sodium, potassium and calcium conductances, and other basic membrane properties, and correlate the resulting changes in intracellular ionic conditions with those in contraction strength. We also plan to make use of these results in analyzing the mechanisms of action of epinephrine and digitalis (or other cardiac glycosides used in heart disease), and of certain other important agents including dilantin and procaine.